Sulfate handling in proximal renal tubular defects

Background Renal tubular disease causes loss of electrolytes and other molecules. One of these electrolytes is sulfate, which is reabsorbed by dedicated transporters (NaS1, encoded by SLC13A1 gene). Still, sulfate is rarely measured in clinical practice, although it is essential for development and functioning of several organ systems. The importance of adequate sulfate stores is emphasized by genetic disorders impairing sulfate metabolism in brain, bone and the endocrine system, causing severe neurodevelopmental disorders, skeletal dysplasia and hormonal imbalance. Low availability due to renal loss of sulfate has also been linked to these disorders. Objective To assess the prevalence of renal sulfate wasting in renal tubular diseases. Methods Sulfate was measured in serum and urine of patients with proximal renal tubular disorders using remnant material obtained during routine check-ups. Fractional excretion of sulfate was calculated alongside plasma sulfate concentrations and cystatin C-based eGFR. Results 14 patients were included in whom 1 to 4 paired measurements of urine and plasma sulfate were available. Five patients had decreased plasma sulfate on at least one occasion; 13 patients had increased fractional excretion in at least one measurement. In patients with cystinosis, during cysteamine treatment plasma sulfate levels were often normal despite increased fractional excretion Conclusion Increased sulfate loss is prevalent in children with proximal tubular defects and sulfate stores can be repleted by oral supplements like cysteamine.